PLA2R1
protein-codingphospholipase A2 receptor 1, the group of C-type lectin domain containing
Gene summary
This gene represents a phospholipase A2 receptor. The encoded protein likely exists as both a transmembrane form and a soluble form. The transmembrane receptor may play a role in clearance of phospholipase A2, thereby inhibiting its action. Polymorphisms at this locus have been associated with susceptibility to idiopathic membranous nephropathy. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLA2R1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007366.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 4 | 7 | |||
| missense | 180 | 16 | 1 | 197 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 190 | 20 | 2 | 212 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_031392.3 | 30 | MANE Select | |
| Ensembl | ENSP00000283243.7 | 30 | MANE Select | |
| RefSeq | NP_001007268.1 | 27 | Standard | |
| RefSeq | NP_001182570.1 | 30 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phagosome - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Acyl chain remodelling of PI
- Acyl chain remodelling of PG
- Metabolism of lipids
Biological Process
- cytokine production
- receptor-mediated endocytosis
- positive regulation of DNA damage response, signal transduction by p53 class mediator
- reactive oxygen species metabolic process
- positive regulation of arachidonic acid secretion
Molecular Function
- transmembrane signaling receptor activity
- carbohydrate binding
- phospholipase binding
Cellular Component
- extracellular region
- plasma membrane
- cell surface
- integral component of membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000283243
- Coding exons
- 30
- Length
- 130603
- Individuals with no LoFs
- 122849
- Homozygous LoFs
- 78
- Heterozygous LoFs
- 2821
- Defined
- 125748
- p
- 0.0116
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.351 | 748 | 775 | 0.965 | 0.0000394 | 9724 |
| Missense (PolyPhen) | 241 | 271.33 | 0.88822 | 3606 | ||
| Synonymous | 0.394 | 263 | 271 | 0.970 | 0.0000144 | 2564 |
| Loss of Function | 2.57 | 60 | 85.7 | 0.700 | 0.00000400 | 1012 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.11 | 0.11 | notable |
| Latino/Admixed American | 0.0084 | 0.0080 | notable |
| Ashkenazi Jewish | 0.048 | 0.048 | notable |
| East Asian | 0.00067 | 0.00065 | rare |
| Finnish | 0.0011 | 0.0011 | notable |
| European (Non-Finnish) | 0.0025 | 0.0025 | notable |
| South Asian | 0.0025 | 0.0025 | notable |
| Other | 0.012 | 0.012 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phosholipase sPLA2-IB/PLA2G1B but not sPLA2- IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2- IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow- derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in proinflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B. {ECO:0000269|PubMed:15611272, ECO:0000269|PubMed:7721806}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.999
- RVIS EVS
- 0.86
- RVIS percentile EVS
- 88.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.157
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |